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Otak dan Neurotransmiter

Hadi Sarosa

Alzheimer’s Disease

Alois Alzhemer (1901), clinical case Auguste D, , ages : 51 years

Clinical (1901)

Cognitive disturbance Disorientation Delusions Aphasia Behavior dyscontrol

Post mortem (1906)

Presenile dementia

Striking generalized cortical atrophy

Unique neuropathological changes

Publication (1911)

Histology

Neurofibrillary tangles (NFT) Neuritic plaques

Matthews B.R. & Miller B.L. (2009) Alzheimer’s disease. In The Behavioral Neurology of Dementia. Miller B.L. &

Boeve B.F. (ed). Cambridge University Press. pp. 56-73.

chromosome 19
chromosome
19
Evolusi Gen Pengalaman Organisme saat ini Situasi saat ini Perilaku saat ini
Evolusi
Gen
Pengalaman
Organisme saat ini
Situasi saat ini
Perilaku saat ini

Interaksi Faktor Genetik dan

Pengalaman

Tyron (1994) : Selective-breeding (maze-bright dan maze-dull)

Asbjörn Fölling (1934): Phenylketonuria (PKU)

Defisiensi fenilalamin hidroksilase mengkonversi fenilalamin menjadi tyrosin, bahan untuk disintesis menjadi dopamin

Behaviour (tingkah laku)
Behaviour (tingkah laku)
  • Menggambarkan fungsi seluruh sistem saraf

Kegiatan motorik bawah sadar

Reflek bawah sadar

Emosi, kesenangan, ketakutan, cemas, sex

Atur fungsi vegetatif

  • Kardiovaskuler,suhu tubuh,

  • Hormonal, metabolisma, berat badan

  • Pusat kenyang, pusat haus.

Fungsi luhur (moral) : Fungsi kognitif

Cognitive function

Cognitive function, an intellectual process by which one becomes aware of, perceives, or

comprehends ideas. It involves all aspects of perception, thinking, reasoning, and remembering.

Mosby's Medical Dictionary, 8th edition. © 2009, Elsevier.

Cognition: means of acquiring and processing information about our selves and our world

COGNITIVE DOMAINS :

Memory (acquiring, retaining, and retrieving new information)

Attention and concentration (particularly divided attention) Information processing (dealing with information gathered by the five senses) Executive functions (planning and prioritizing)

Visuospatial functions (visual perception and constructional abilities)

Verbal fluency (word-finding)

Each hemisphere of the cortex can further be divided into four lobes:

Occipital - visual processing

Parietal - movement,

orientation, calculation, recognition

Temporal - sound and

speech processing, aspects of memory

Frontal - thinking,

conceptualisation,

planning.

Cortical Functional Networks Inferior Parietal Lobus Dorsomedial Prefrontal Cortex Posteromedial Cortex : Hippocampus Retrosplenial Cortex Parahippocampal
Cortical Functional Networks
Inferior
Parietal
Lobus
Dorsomedial
Prefrontal
Cortex
Posteromedial Cortex :
Hippocampus
Retrosplenial Cortex
Parahippocampal
Posterior Cingulate Cortex
Cortex
Precuneus
Ventromedial
Prefrontal
Cortex
Lateral
Temporal
Cortex
Glutamatergic excitatory input
Glutamatergic excitatory input

Frontal Lobe

Conscientiousness Judgments

Frontal Lobe • Conscientiousness Judgments • • • • How we initiate activity in response to

How we initiate activity in response to our environment. Controls our emotional response. Controls our expressive language.

Assigns meaning to the words we choose (abstract thought)

Attention span Involves word associations (language planning) Memory for habits and motor activities (short term memory)

Motor cortexVoluntary movement Impulse control Perseverance

Frontal Lobe DeficitProblems

Loss of simple movement of various body parts (Paralysis).

Inability to plan a sequence of complex movements needed to complete multi-stepped tasks, such as making coffee (Sequencing).

Loss of spontaneity in interacting with others.

Loss of flexibility in thinking.

Persistence of a single thought (Perseveration).

Inability to focus on task (Attending).

Mood changes (Emotionally Labile).

Changes in social behavior.

Changes in personality.

Difficulty with problem solving.

Inablility to express language (Broca's Aphasia).

Frontal Lobe Deficit — Problems • Loss of simple movement of various body parts ( Paralysis

Parietal Lobe Function

Parietal Lobe Function • Location for visual attention. • Location for touch perception. • Goal directed

Location for visual attention. Location for touch perception. Goal directed voluntary movements. Manipulation of objects.

Integration of different senses that allows for understanding a single concept.

Parietal LobeProblems resulting from deficit

Inability to attend to more than one object at a time.

Inability to name an object (Anomia).

Inability to locate the words for writing (Agraphia).

Problems with reading (Alexia).

Difficulty with drawing objects.

Difficulty in distinguishing left from right.

Difficulty with doing mathematics (Dyscalculia).

Lack of awareness of certain body parts and/or surrounding space (Apraxia) that leads to difficulties in self-care.

Inability to focus visual attention.

Difficulties with eye and hand coordination.

Parietal Lobe — Problems resulting from deficit • Inability to attend to more than one object

Temporal Lobe Function

Hearing ability Memory acquisition Some visual perceptions Categorization of objects.

Temporal Lobe Function • Hearing ability • Memory acquisition • Some visual perceptions • Categorization of

Temporal Lobe DeficitsProblems

Difficulty in recognizing faces (Prosopagnosia).

Difficulty in understanding spoken words (Wernicke's Aphasia).

Disturbance with selective attention to what we see and hear.

Difficulty with identification of, and verbalization

about objects.

Short-term memory loss.

Interference with long-term memory

Increased or decreased interest in sexual behavior.

Inability to catagorize objects (Catagorization). Right lobe damage can cause persistant talking.

Increased aggressive behavior.

   

Occipital Lobe

Function

Vision

Occipital Lobe Function • Vision

Occipital Lobe Deficits--Problems

Defects in vision (Visual Field Cuts). Difficulty with locating objects in environment. Difficulty with identifying colors (Color Agnosia). Production of hallucinations Visual illusions - inaccurately seeing objects. Word blindness - inability to recognize words. Difficulty in recognizing drawn objects.

Inability to recognize movement of an object (Movement Agnosia).

Difficulties with reading and writing.

Occipital Lobe Deficits--Problems • Defects in vision ( Visual Field Cuts ). • Difficulty with locating
 Amygdala, Hippocampus dan nuclei septal  Fungsi • Pengaturan olfactori • Respon autonom • Perilaku
Amygdala,
Hippocampus dan
nuclei septal
Fungsi
• Pengaturan olfactori
• Respon autonom
• Perilaku sexual
• Emosi : marah, takut
• Motivasi

Komunikasi Neuron di Otak

  • A. IMPULS LISTRIK

    • B. ZAT KIMIA : NEUROTRANSMITTER

      • 1. Asetil kolin

      • 2. Asam amino

        • Gama-aminobutyric acid (GABA)

        • Glutamat

        • Aspartat

        • Glycine

  • 3. Monoamine

    • Dopamin

    • Histamin

    • NE

  • Serotonin

    4. Neuropeptide

    • Somatostatin

    • Endorphin

    • Enkaphalin

    • substance P

    Otak : listrik & Neurotransmitter

    Otak : listrik & Neurotransmitter

    Potensial membran

    Potensial membran

    Neurotransmitter

    Neurotransmitter

    Neurotransmiter

       

    Glutamat

     

    eksitatorik

    Aspartat

       

    Asam Amino

    Glisin

    Gammaaminobutyric acid (GABA)

     

    Inhibitorik

    Molekul Kecil Konvensional

       

    dopamin

     

    Catecholamines ( Tirosin)

    epinefrin

    Mono Amine

    norepinefrin

    Indolalamin (Tryptophan)

    serotonin

    Asetilkolin

    Asetilkolin

     
     

    Gas gas yang dapat

    Oksida Nitrit

    Molekul Kecil tak

    larut

    Karbon monosida

    Konvensional

    Endokanabinoida

    Anandamida

       

    Peptida pituitaria

    Molekul Besar

    Neuropeptide

    Peptida hipotalamik

    Peptida opiat

    Neurotransmiter Sistem ekstrapiramidal

    Neurotransmiter

    Sistem ekstrapiramidal

    Neurotransmiter Sistem ekstrapiramidal
    Neurotransmiter Sistem ekstrapiramidal

    Neurotransmitter

    The Dopamine Pathways

    Nigrostriatal pathway Substantia Nigra to Striatum . Motor control . Death of neurons in this pathway
    Nigrostriatal pathway
    Substantia Nigra to Striatum
    . Motor control
    . Death of neurons in
    this pathway can result in
    Parkinson's Disease
    Tuberoinfundibular pathway
    Hypothalamus to Pituitary gland
    . Hormonal regulation
    Mesolimbic and Mesocortical pathways
    Ventral Tegmental Area to Nucleus
    Accumbens, Amygdala & Hippocampus,
    and Prefrontal Cortex
    . Memory
    . Motivation and emotional response
    . Reward and desire
    . Addiction
    . Can cause hallucinations and schizophrenia if
    not functioning properly
    . Maternal behavior (nurturing)
    . Pregnancy
    . Sensory processes
    The Serotonin Pathways  Dihasilkan oleh nuclei Raphe  Dipengaruhi oleh obat : Amphetamin, alkohol, cocaine
    The Serotonin Pathways
    Dihasilkan oleh nuclei
    Raphe
    Dipengaruhi oleh obat :
    Amphetamin, alkohol,
    cocaine
    Raphe Nuclei
    Berperan penting dalam
    proses di otak : pengaturan
    temperatur, mood, lapar,
    nyeri dan tidur

    Problems with the serotonin pathway can cause obsessive- compulsive disorder, anxiety disorders, and depression. Most of the drugs used to treat depression today work by increasing serotonin

    levels in the brain.

    Glutamate and GABA (gamma-aminobutyric acid) are the brain's major "workhorse" neurotransmitters. Over half of all brain

    Glutamate and GABA (gamma-aminobutyric acid) are the brain's major

    "workhorse"

    neurotransmitters. Over half of all brain synapses

    release glutamate, and 30-

    40% of all brain synapses release GABA.

    Alcohol

    Caffeine

    decreases

    inhibits

    glutamate

    GABA

    activity

    release

    PCP

    "angel

    Tranquilize

    dust"

    Caffeine

    Alcohol

    rs increase

    increases

    increases

    increases

    GABA

    glutamate

    glutamate

    GABA

    activity

    activity

    activity

    activity

    Sedatif-Hipnotik dan Ansiolitik

    Golongan Barbiturat

    meningkatkan respon GABA

    membuka kanal ion Cl- meski tanpa GABA

    Golongan

    Benzodiazepin

    Sedatif-Hipnotik dan Ansiolitik • Golongan Barbiturat – meningkatkan respon GABA – membuka kanal ion Cl- meski

    Anti Depresan

    Depresi : Kadar dopamin, serotonin dan NE menurun

    1. Serotonin Spesific Reuptake inhibitor (SSRI)

    misal : Fluoxetin

    2. Heterosiklik

    mengeblok reuptake serotonin dan norepinefrin, dan sebagai antagonis reseptor muskarinik. sehingga kadar serotonin dan NE tinggi (misal :

    desipramin, imipramin) 3. Serotonin Norephinefrin Reuptake Inhibitor (SNRI)

    Anti Depresan

    4. MAO inhibitor menghambat MAO

    menghancurkan serotonin, dopamin dan NE (misal :

    isokarboksamid) 5. Lain-lain

    antagonis reseptor alfa 2 presinaptiksekresi serotonin dan NE meningkat (misal :

    Mirtazapiin)

    Anti Depresan 4 . MAO inhibitor menghambat MAO menghancurkan serotonin, dopamin dan NE (misal : isokarboksamid)

    Antipsikotik (neuroleptik)

    Psikotik : Kadar Dopamin & Serotonin >>

    Typical neuroleptik

    Untuk mengobati gejala positif

    dengan menurunkan dopamin Mekanisme :

    mengeblok reseptor dopamin, kolinergik muskarinik, alfa adrenergik dan H-1 histaminergik

    Contoh :

    Klorpromasin, Haloperidol (potensi besar namun efek samping paling besar yaitu parkinson), Acetofenasin

    Atypical, 5-HT DA Antagonist

    Untuk mengobati gejala postif & negatif :

    menghambat reseptor dopamin dan serotonin

    Mekanisme :

    antagonis serotonin-dopamin, mengeblok reseptor kolinergik muskarinik, alfa-1 adrenergik dan H-1 histaminergik

    Contoh :

    Clozapine, Quetiapine

    Parkinson

    Ganglia Basalis : serabut dopaminergik << asetyl cholin >>

    • 1. Pengganti dopamin (terapi utama)

      • a. levodopa : prekursor metabolik dopamin

      • b. karbidopa : inhibitor dekarboksilase dopamin -> menurunkan metabolisme levodopa -> kadar levodopa meningkat

    • c. tolkapon : inhibitor COMT (Catechol-O-Methyl-transferase)

    sehingga

    levodopa bisa hidup lebih lama (waktu paro lebih panjang) dan kadarnya dalam

    darah meningkat

    • 2. Agonis reseptor dopamin (misal : bromokriptin, pergolid, pramipexole)

    • 3. Antikolinergik (misal : triheksifenidil, benzotropin)

    NEUROPLASTISITAS OTAK

    Kemampuan Otak untuk berubah dan mengubah

    strukturnya sebagai Respon terhadap rangsangan dari luar (lingkungan)

    Menunjukkan bahwa situasi dan lingkungan yang tepat Dapat memberikan pengaruh kuat terhadap perubahan otak

    Keadaan lingkungan yang berkaitan

    dengan Neuroplastisitas Otak

    1.Kegiatan Fisik (Voluntary Gross Motor)

    2.Pembelajaran baru, menantang dan penuh makna 3.Kesulitan yang logis (tidak bikin kacau)

    4.Stresor yang dapat dikelola dengan baik

    5.Dukungan sosial (rumah dan komunitas) 6.Nutrisi yang baik 7.Waktu yang mencukupi